Autism spectrum disorder (ASD)

Autism spectrum disorder is a neurodevelopmental condition that affects how a person communicates, interacts socially, and experiences the world. It is described by the U.S. Centers for Disease Control and Prevention as a developmental disability associated with differences in brain development and behavior, typically beginning in early childhood and lasting throughout life.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), ASD is defined by two core domains:

• Persistent deficits in social communication and social interaction across multiple contexts (for example, difficulty with back-and-forth conversation, understanding nonverbal cues, or developing and maintaining relationships).
• Restricted, repetitive patterns of behavior, interests, or activities (such as repetitive movements or speech, insistence on sameness, highly focused interests, or atypical responses to sensory input).

These features must begin in the early developmental period, cause clinically significant impairment in social, occupational, or other important areas of functioning, and cannot be better explained by intellectual disability alone.

The term “spectrum” reflects wide variability in strengths and support needs. Some autistic individuals have co-occurring intellectual disability or language impairment; others have average or above-average intelligence but significant social-communication differences, sensory sensitivities, or executive-function challenges.

Causes and risk factors

There is no single known cause of autism spectrum disorder. Current evidence indicates that ASD arises from a complex interplay of genetic susceptibility and environmental (non-genetic) factors that affect brain development, particularly during early embryonic and fetal life.

Genetic factors

• ASD tends to run in families, and large twin and family studies estimate that about 80% of the overall liability to autism is heritable, meaning that genetic differences account for most of the variation in risk across the population.
• Hundreds of genes have now been associated with ASD, including rare variants of large effect and more common variants of smaller effect. Examples include genes involved in synaptic function and brain development such as CHD8, SCN2A, and others.
• In some individuals, autism occurs as part of a broader genetic syndrome such as fragile X syndrome, tuberous sclerosis complex, Rett syndrome, or PTEN-hamartoma tumor syndrome. When state-of-the-art genetic testing (chromosomal microarray, exome/genome sequencing, and targeted tests) is applied, a likely genetic explanation can be found in roughly 10–30% of children with ASD, depending on the population and testing strategy.

Even when a specific genetic variant is identified, it usually confers increased risk rather than guaranteeing that autism will occur, and different people with the same variant may have different developmental outcomes.

Environmental and perinatal factors

Non-genetic (environmental) factors appear to make a smaller but important contribution to ASD risk. These factors generally modify risk in genetically susceptible individuals rather than acting as sole causes. Examples with supportive evidence include:

• Advanced parental age, especially higher maternal or paternal age at conception, which has been associated with a modestly increased risk of ASD in several large epidemiologic studies.
• Extreme prematurity and very low birthweight, which are associated with higher rates of a variety of neurodevelopmental conditions, including autism.
• Certain maternal medical conditions during pregnancy, such as pre-existing diabetes, gestational diabetes, or obesity, which have been linked to increased ASD risk in observational studies.
• In-utero exposure to specific medications or infections, notably:
  • Antiseizure drugs containing valproate (valproic acid), which are associated with a significantly increased risk of neurodevelopmental disorders including ASD when used in pregnancy.
  • Certain congenital infections (for example, rubella or cytomegalovirus), which can cause broader patterns of brain injury that may include autism among other neurologic outcomes.

Many other environmental factors have been studied (including air pollution, prenatal stress, and nutritional factors), but for most, evidence is still limited or inconsistent, and effect sizes—when present—tend to be small compared with genetic influences.

What does not cause autism?

• Large, well-designed studies in multiple countries have found no association between the measles-mumps-rubella (MMR) vaccine and autism, even in high-risk children. The most cited large Danish cohort study followed more than 650,000 children and found that MMR vaccination did not increase ASD risk.
• Parenting style, ordinary psychological stress, and social factors do not cause autism. Early theories blaming “refrigerator mothers” have been definitively rejected and are not supported by current science.

In summary, autism spectrum disorder is a common, highly heritable neurodevelopmental condition in which rare and common genetic variants play a major role, while certain environmental and perinatal exposures modestly influence risk. For most individuals, a single “cause” cannot be identified; instead, ASD reflects the combined effects of many genetic and environmental influences on early brain development.